Cannabinoids of natural origin are compounds derived from plants commonly known as marijuana. Among the several dozen cannabinoid compounds characterizing marijuana, tetrahydrocannabinols (THC), and Δ9-tetrahydrocannabinol (Δ9-THC) in particular, are considered to be those most active. These compounds possess several properties, e.g., an analgesic effect, an anti-inflammatory activity, the reduction of the blood and intraocular pressure, and an antiemetic activity, that may be therapeutic both in mammals and in human beings.
Additionally, such preparations derived from natural origin have been effectively used as anti-emetics for treatment of nausea and vomiting and for enhancement of appetite, mainly in AIDS patients. (Mechoulam, R., “Cannabinoids as Therapeutic Agents” CRC Press, Boca Raton, Fla. 1-19, 1986).
The pharmacological action of cannabinoids appears directly correlated to their affinity towards two different classes of specific receptors belonging to the family of the “G protein-coupled” receptors: the CB1 receptors, located in the central nervous system besides that in peripheral tissues, and the CB2 receptors, found in the cerebellum (Q. J. Lu et al.; Visual Neurosci.; 2000, 17, 91-95) but which are mostly found in peripheral tissues (M. Glass; Progr. Neuro-Psychopharmacol. &Biol. Psychiat.; 2001, 25, 743-765). In the brain, the CB1 receptors are found in the hippocampus, in the cortical regions, in the cerebellum, and inside the basal ganglia. Among the peripheral tissues wherein the CB1 receptors have been found, the testicles, the small intestine, the vesica, the deferent duct can be mentioned. CB1 receptors have also been identified in the human eye, variously in the retina, in the iris, and in the ciliary body (A. Porcella et al.; Molecular Brain Research; 1998, 58, 240-245; A. Porcella et al.; European Journal of Neuroscience; 2000, 12, 1123-1127).
The CB2 receptors are largely located in the marginal zones of the spleen, in tonsils, in several cells of the immune system, as macrophages, monocytes, the cells of the bone marrow, of thymus, and of pancreas. Other cells of the immune system having CB2 receptors are T4 and T8 cells, the polymorphonucleated leucocytes, in particular the cells called “natural killers” and lymphocytes B.
The native active constituent, delta 9-tetrahydrocannabinol (Δ9-THC), is synthetically produced, prescribed, and sold today. In the U.S. and Canada, (Δ9-THC) is nominated as “dronabinol” under the mark “MARINOL®” by Solvay Pharmaceuticals and, under license, by PAR Pharmaceuticals. The U.S. Food and Drug Administration has approved MARINOL® for the treatment of anorexia and wasting in AIDS patients, as well as for refractory nausea and vomiting by patients undergoing chemotherapy.